Chronic infections with the hepatitis C virus (HCV) are a major global health issue. Viral replication is restricted to hepatocytes, and occurs for decades at high replication rates. Over the last decade, it became accepted that HCV-specific CD4+ and CD8+ T cells are crucial for protective immunity to HCV. However, a characteristic feature of persistent HCV infection is the dysfunctional T cell response, and over recent years enormous progress has been made in understanding the mechanisms that dampen the antiviral T cell responses in blood and liver of chronic HCV patients and also impact disease progression.